RESUMEN
We treated a 27-year-old patient with Duchenne's muscular dystrophy (DMD) with recombinant adeno-associated virus (rAAV) serotype 9 containing dSaCas9 (i.e., "dead" Staphylococcus aureus Cas9, in which the Cas9 nuclease activity has been inactivated) fused to VP64; this transgene was designed to up-regulate cortical dystrophin as a custom CRISPR-transactivator therapy. The dose of rAAV used was 1×1014 vector genomes per kilogram of body weight. Mild cardiac dysfunction and pericardial effusion developed, followed by acute respiratory distress syndrome (ARDS) and cardiac arrest 6 days after transgene treatment; the patient died 2 days later. A postmortem examination showed severe diffuse alveolar damage. Expression of transgene in the liver was minimal, and there was no evidence of AAV serotype 9 antibodies or effector T-cell reactivity in the organs. These findings indicate that an innate immune reaction caused ARDS in a patient with advanced DMD treated with high-dose rAAV gene therapy. (Funded by Cure Rare Disease.).
Asunto(s)
Distrofina , Terapia Genética , Distrofia Muscular de Duchenne , Síndrome de Dificultad Respiratoria , Transgenes , Adulto , Humanos , Anticuerpos , Distrofina/genética , Terapia Genética/efectos adversos , Terapia Genética/métodos , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/terapia , Síndrome de Dificultad Respiratoria/etiología , Síndrome de Dificultad Respiratoria/inmunología , Transgenes/genética , Transgenes/inmunología , Resultado Fatal , Inmunidad Innata/genética , Inmunidad Innata/inmunologíaRESUMEN
Melioidosis, caused by the bacterium Burkholderia pseudomallei, is an uncommon infection that is typically associated with exposure to soil and water in tropical and subtropical environments. It is rarely diagnosed in the continental United States. Patients with melioidosis in the United States commonly report travel to regions where melioidosis is endemic. We report a cluster of four non-travel-associated cases of melioidosis in Georgia, Kansas, Minnesota, and Texas. These cases were caused by the same strain of B. pseudomallei that was linked to an aromatherapy spray product imported from a melioidosis-endemic area.
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Aromaterapia/efectos adversos , Burkholderia pseudomallei/aislamiento & purificación , Brotes de Enfermedades , Melioidosis/epidemiología , Aerosoles , Encéfalo/microbiología , Encéfalo/patología , Burkholderia pseudomallei/genética , COVID-19/complicaciones , Preescolar , Resultado Fatal , Femenino , Genoma Bacteriano , Humanos , Pulmón/microbiología , Pulmón/patología , Masculino , Melioidosis/complicaciones , Persona de Mediana Edad , Filogenia , Choque Séptico/microbiología , Estados Unidos/epidemiologíaRESUMEN
Subacute sclerosing panencephalitis (SSPE) is a rare but fatal late neurological complication of measles, caused by persistent measles virus (MeV) infection of the central nervous system. There are no drugs approved for the treatment of SSPE. Here, we followed the clinical progression of a 5-year-old SSPE patient after treatment with the nucleoside analog remdesivir, conducted a post-mortem evaluation of the patient's brain, and characterized the MeV detected in the brain. The quality of life of the patient transiently improved after the first two courses of remdesivir, but a third course had no further clinical effect, and the patient eventually succumbed to his condition. Post-mortem evaluation of the brain displayed histopathological changes including loss of neurons and demyelination paired with abundant presence of MeV RNA-positive cells throughout the brain. Next-generation sequencing of RNA isolated from the brain revealed a complete MeV genome with mutations that are typically detected in SSPE, characterized by a hypermutated M gene. Additional mutations were detected in the polymerase (L) gene, which were not associated with resistance to remdesivir. Functional characterization showed that mutations in the F gene led to a hyperfusogenic phenotype predominantly mediated by N465I. Additionally, recombinant wild-type-based MeV with the SSPE-F gene or the F gene with the N465I mutation was no longer lymphotropic but instead efficiently disseminated in neural cultures. Altogether, this case encourages further investigation of remdesivir as a potential treatment of SSPE and highlights the necessity to functionally understand SSPE-causing MeV.IMPORTANCEMeasles virus (MeV) causes acute, systemic disease and remains an important cause of morbidity and mortality in humans. Despite the lack of known entry receptors in the brain, MeV can persistently infect the brain causing the rare but fatal neurological disorder subacute sclerosing panencephalitis (SSPE). SSPE-causing MeVs are characterized by a hypermutated genome and a hyperfusogenic F protein that facilitates the rapid spread of MeV throughout the brain. No treatment against SSPE is available, but the nucleoside analog remdesivir was recently demonstrated to be effective against MeV in vitro. We show that treatment of an SSPE patient with remdesivir led to transient clinical improvement and did not induce viral escape mutants, encouraging the future use of remdesivir in SSPE patients. Functional characterization of the viral proteins sheds light on the shared properties of SSPE-causing MeVs and further contributes to understanding how those viruses cause disease.
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Adenosina Monofosfato , Alanina , Virus del Sarampión , Sarampión , Panencefalitis Esclerosante Subaguda , Proteínas Virales , Preescolar , Humanos , Adenosina Monofosfato/administración & dosificación , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Alanina/administración & dosificación , Alanina/análogos & derivados , Alanina/uso terapéutico , Autopsia , Encéfalo/metabolismo , Encéfalo/patología , Encéfalo/virología , Progresión de la Enfermedad , Resultado Fatal , Genoma Viral/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Sarampión/complicaciones , Sarampión/tratamiento farmacológico , Sarampión/virología , Virus del Sarampión/efectos de los fármacos , Virus del Sarampión/genética , Virus del Sarampión/metabolismo , Proteínas Mutantes/análisis , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Calidad de Vida , ARN Viral/análisis , ARN Viral/genética , Panencefalitis Esclerosante Subaguda/tratamiento farmacológico , Panencefalitis Esclerosante Subaguda/etiología , Panencefalitis Esclerosante Subaguda/virología , Proteínas Virales/análisis , Proteínas Virales/genética , Proteínas Virales/metabolismoRESUMEN
We report a fatal case of New Delhi metallo-ß-lactamase (NDM)-producing Escherichia coli in a bacteremic patient with sequential failure of aztreonam plus ceftazidime-avibactam followed by cefiderocol. Acquired resistance was documented phenotypically and mediated through preexisting and acquired mutations. This case highlights the need to rethink optimal treatment for NDM-producing organisms.
Asunto(s)
Antibacterianos , Compuestos de Azabiciclo , Aztreonam , Bacteriemia , Cefiderocol , Ceftazidima , Cefalosporinas , Combinación de Medicamentos , Infecciones por Escherichia coli , Escherichia coli , Insuficiencia del Tratamiento , beta-Lactamasas , Humanos , Compuestos de Azabiciclo/uso terapéutico , Compuestos de Azabiciclo/administración & dosificación , beta-Lactamasas/genética , beta-Lactamasas/metabolismo , Aztreonam/uso terapéutico , Aztreonam/administración & dosificación , Aztreonam/farmacología , Ceftazidima/uso terapéutico , Ceftazidima/administración & dosificación , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Escherichia coli/enzimología , Escherichia coli/aislamiento & purificación , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/microbiología , Resultado Fatal , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Cefalosporinas/uso terapéutico , Cefalosporinas/administración & dosificación , Pruebas de Sensibilidad Microbiana , Masculino , Farmacorresistencia Bacteriana MúltipleRESUMEN
We report findings in five patients who presented with venous thrombosis and thrombocytopenia 7 to 10 days after receiving the first dose of the ChAdOx1 nCoV-19 adenoviral vector vaccine against coronavirus disease 2019 (Covid-19). The patients were health care workers who were 32 to 54 years of age. All the patients had high levels of antibodies to platelet factor 4-polyanion complexes; however, they had had no previous exposure to heparin. Because the five cases occurred in a population of more than 130,000 vaccinated persons, we propose that they represent a rare vaccine-related variant of spontaneous heparin-induced thrombocytopenia that we refer to as vaccine-induced immune thrombotic thrombocytopenia.
Asunto(s)
Autoanticuerpos/sangre , Vacunas contra la COVID-19/efectos adversos , Factor Plaquetario 4/inmunología , Trombocitopenia/etiología , Trombosis/etiología , Adulto , Enfermedades Autoinmunes/etiología , Análisis Químico de la Sangre , ChAdOx1 nCoV-19 , Ensayo de Inmunoadsorción Enzimática , Resultado Fatal , Femenino , Humanos , Masculino , Persona de Mediana Edad , Agregación Plaquetaria , Recuento de PlaquetasRESUMEN
BACKGROUND: Several cases of unusual thrombotic events and thrombocytopenia have developed after vaccination with the recombinant adenoviral vector encoding the spike protein antigen of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (ChAdOx1 nCov-19, AstraZeneca). More data were needed on the pathogenesis of this unusual clotting disorder. METHODS: We assessed the clinical and laboratory features of 11 patients in Germany and Austria in whom thrombosis or thrombocytopenia had developed after vaccination with ChAdOx1 nCov-19. We used a standard enzyme-linked immunosorbent assay to detect platelet factor 4 (PF4)-heparin antibodies and a modified (PF4-enhanced) platelet-activation test to detect platelet-activating antibodies under various reaction conditions. Included in this testing were samples from patients who had blood samples referred for investigation of vaccine-associated thrombotic events, with 28 testing positive on a screening PF4-heparin immunoassay. RESULTS: Of the 11 original patients, 9 were women, with a median age of 36 years (range, 22 to 49). Beginning 5 to 16 days after vaccination, the patients presented with one or more thrombotic events, with the exception of 1 patient, who presented with fatal intracranial hemorrhage. Of the patients with one or more thrombotic events, 9 had cerebral venous thrombosis, 3 had splanchnic-vein thrombosis, 3 had pulmonary embolism, and 4 had other thromboses; of these patients, 6 died. Five patients had disseminated intravascular coagulation. None of the patients had received heparin before symptom onset. All 28 patients who tested positive for antibodies against PF4-heparin tested positive on the platelet-activation assay in the presence of PF4 independent of heparin. Platelet activation was inhibited by high levels of heparin, Fc receptor-blocking monoclonal antibody, and immune globulin (10 mg per milliliter). Additional studies with PF4 or PF4-heparin affinity purified antibodies in 2 patients confirmed PF4-dependent platelet activation. CONCLUSIONS: Vaccination with ChAdOx1 nCov-19 can result in the rare development of immune thrombotic thrombocytopenia mediated by platelet-activating antibodies against PF4, which clinically mimics autoimmune heparin-induced thrombocytopenia. (Funded by the German Research Foundation.).
Asunto(s)
Autoanticuerpos/sangre , Vacunas contra la COVID-19/efectos adversos , Factor Plaquetario 4/inmunología , Trombocitopenia/etiología , Trombosis/etiología , Adulto , Enfermedades Autoinmunes/etiología , Análisis Químico de la Sangre , ChAdOx1 nCoV-19 , Coagulación Intravascular Diseminada/etiología , Ensayo de Inmunoadsorción Enzimática , Resultado Fatal , Femenino , Humanos , Hemorragias Intracraneales/etiología , Masculino , Persona de Mediana Edad , Activación Plaquetaria , Trombocitopenia/inmunología , Trombosis/inmunología , Adulto JovenRESUMEN
During the 2018-2020 Ebola virus disease (EVD) outbreak in North Kivu province in the Democratic Republic of Congo, EVD was diagnosed in a patient who had received the recombinant vesicular stomatitis virus-based vaccine expressing a ZEBOV glycoprotein (rVSV-ZEBOV) (Merck). His treatment included an Ebola virus (EBOV)-specific monoclonal antibody (mAb114), and he recovered within 14 days. However, 6 months later, he presented again with severe EVD-like illness and EBOV viremia, and he died. We initiated epidemiologic and genomic investigations that showed that the patient had had a relapse of acute EVD that led to a transmission chain resulting in 91 cases across six health zones over 4 months. (Funded by the Bill and Melinda Gates Foundation and others.).
Asunto(s)
Ebolavirus/genética , Fiebre Hemorrágica Ebola/transmisión , Adulto , Teorema de Bayes , República Democrática del Congo/epidemiología , Vacunas contra el Virus del Ébola/inmunología , Ebolavirus/aislamiento & purificación , Resultado Fatal , Genoma Viral , Fiebre Hemorrágica Ebola/diagnóstico , Fiebre Hemorrágica Ebola/epidemiología , Fiebre Hemorrágica Ebola/terapia , Humanos , Masculino , Mutación , Filogenia , ARN Viral/sangre , RecurrenciaRESUMEN
Two cases of pediatric lung cancer (in 23-month-old and 6-year-old boys) resulting from mother-to-infant transmission of uterine cervical tumors were incidentally detected during routine next-generation sequencing of paired samples of tumor and normal tissue. Spontaneous regression of some lesions in the first child and slow growth of the tumor mass in the second child suggested the existence of alloimmune responses against the transmitted tumors. Immune checkpoint inhibitor therapy with nivolumab led to a strong regression of all remaining tumors in the first child. (Funded by the Japan Agency for Medical Research and Development and others; TOP-GEAR UMIN Clinical Trials Registry number, UMIN000011141.).
Asunto(s)
Adenocarcinoma Mucinoso/etiología , Carcinoma Neuroendocrino/etiología , Neoplasias Pulmonares/etiología , Complicaciones Neoplásicas del Embarazo , Neoplasias del Cuello Uterino , Adenocarcinoma Mucinoso/diagnóstico por imagen , Adenocarcinoma Mucinoso/genética , Adulto , Carcinoma Neuroendocrino/diagnóstico por imagen , Carcinoma Neuroendocrino/genética , Carcinoma de Células Escamosas/patología , Niño , Resultado Fatal , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Lactante , Pulmón/diagnóstico por imagen , Pulmón/patología , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Madres , Embarazo , Vagina , Secuenciación del ExomaRESUMEN
Significant progress has been achieved in enhancing early outcomes for individuals with maple syrup urine disease (MSUD), a rare metabolic disorder that leads to the accumulation of branched-chain amino acids leucine, isoleucine, and valine, where leucine is known as the primary neurotoxic metabolite. Newborn screening is helpful in early diagnosis and implementation of dietary treatment, thus reducing neurological deterioration and complications in young children. However, patients face the life-long challenge of maintaining metabolic control through adherence to a strict low-leucine diet to avoid long-term consequences of chronic hyperleucinemia, which include cognitive deficits, mood disorders, and movement disorders. This case report exemplifies the complex involvement of MSUD in adult survivors. Despite presenting early in life, the patient thrived until the onset of psychiatric symptoms. The subject of this case is a 25-year-old woman with MSUD, who remained in her usual state of health until presentation to the emergency department (ED) with psychosis and altered mental status. However, due to a lack of medical records and poor communication, there was a delay in considering MSUD as a primary cause of her psychiatric symptoms. Although a genetics consultation was later arranged and efforts were made to decrease plasma leucine to the therapeutic range, these interventions proved inadequate in halting her deterioration in health. Her condition worsened within 72 h, culminating in her untimely death. This case emphasizes the comorbidity of psychiatric involvement in MSUD, which contributes to metabolic decompensation that can lead to cerebral edema and death. This case also highlights the pressing need for enhanced strategies for the acute management and long-term care of MSUD patients with psychiatric involvement, particularly in scenarios where mental disturbance could lead to noncompliance.
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Enfermedad de la Orina de Jarabe de Arce , Trastornos Psicóticos , Humanos , Femenino , Trastornos Psicóticos/genética , Trastornos Psicóticos/patología , Enfermedad de la Orina de Jarabe de Arce/genética , Enfermedad de la Orina de Jarabe de Arce/complicaciones , Adulto , Resultado Fatal , Leucina/sangreRESUMEN
Neonatal pulmonary hemorrhage is a late manifestation of various diseases. Premature delivery and low body weight are frequently observed as high-risk factors, characterized by acute onset, rapid progression, and high mortality rates. Pulmonary hemorrhage caused by cytomegalovirus infection in newborns with normal immune function is a rare occurrence. This case report focuses on a term neonate with normal birth weight who presented solely with nasal obstruction shortly after birth. However, 4 days after birth, the newborn experienced a sudden onset of blood gushing from both the mouth and nasal cavity. The patient was diagnosed with gastrointestinal bleeding, neonatal pneumonia and neonatal lung consolidation. And he was discharged after ten days of symptomatic treatment. However, upon returning home, the patient experienced a sudden onset of bleeding from the mouth and nose, leading to his untimely demise. Subsequent autopsy revealed the presence of pulmonary hemorrhage in newborn, which presented as interstitial pneumonia. The cause of pulmonary hemorrhage is cytomegalovirus infection. This case emphasizes the importance of pediatricians enhancing their skills in differentiating pulmonary hemorrhage, especially from cytomegalovirus pneumonia.
Asunto(s)
Infecciones por Citomegalovirus , Hemorragia , Humanos , Infecciones por Citomegalovirus/complicaciones , Infecciones por Citomegalovirus/diagnóstico , Recién Nacido , Masculino , Resultado Fatal , Hemorragia/etiología , Citomegalovirus , Pulmón/patología , Pulmón/diagnóstico por imagen , Pulmón/virología , Neumonía Viral/complicaciones , Neumonía Viral/diagnóstico , Neumonía Viral/virología , Autopsia , Enfermedades Pulmonares/virología , Enfermedades Pulmonares/etiologíaRESUMEN
We describe the case of a 57-year-old male with jaundice, abdominal distension and fatigue. He was diagnosed as chronic active Epstein-Barr virus infection (CAEBV) due to intermittent elevated liver enzymes, hepatosplenomegaly and pancytopenia, with persistent positive of EBV biomarkers in blood and also positive in liver tissue. The patient was reinfected by SARS-CoV-2 within 2 months companied with CAEBV. The patient's second infection with SARS-CoV-2 led to the aggravated liver dysfunction with pneumonia and re-admission. After receiving symptomatic treatment, the patient showed significantly improvement of symptoms with partially restoration of liver function. After discharge, the patient's health status continued to deteriorate and eventually died. The instances of SARS-CoV-2 co-infection with the original chronic virus are not uncommon, but the exact mechanism of EBV and SARS-CoV-2 coinfection and the relationship between them are still unclear. Since co-infection of SARS-CoV-2 with original chronic virus might affect each other and lead disease aggravated and complicated, it is necessary to differentiate in the diagnosis of disease and it is important to be aware of the re-infection signs of SARS-CoV-2 in people with chronic virus infection diseases, as well as the risk of co-infection of SARS-CoV-2 with other viruses.
Asunto(s)
COVID-19 , Coinfección , Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Reinfección , SARS-CoV-2 , Humanos , Masculino , COVID-19/diagnóstico , COVID-19/complicaciones , COVID-19/virología , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/virología , Persona de Mediana Edad , Reinfección/virología , Reinfección/diagnóstico , Coinfección/virología , Coinfección/diagnóstico , Herpesvirus Humano 4/genética , Enfermedad Crónica , Resultado FatalRESUMEN
The scientific literature contains little reliable data regarding new psychoactive substances and designer drugs, making it difficult to assess toxic blood levels and potentially lethal threshold. Here, we report a fatal co-intoxication involving two uncommon drugs â alpha-methyltryptamine (AMT) and 5-(2-methylaminopropyl)-benzofuran (5-MAPB) â combined with exposure to benzodiazepines, ephedrine, and norephedrine. AMT and 5-MAPB were quantified using ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC/MS-MS), revealing concentrations of AMT 4690 ng/mL and 5-MAPB 101 ng/mL in postmortem peripheral blood. We additionally reviewed the literature to help interpret the likely roles of these molecules in the occurrence of death.
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Benzofuranos , Humanos , Benzofuranos/envenenamiento , Benzofuranos/sangre , Benzofuranos/análisis , Masculino , Espectrometría de Masas en Tándem , Drogas de Diseño/análisis , Drogas de Diseño/envenenamiento , Cromatografía Líquida de Alta Presión , Adulto , Resultado Fatal , Toxicología Forense , PropilaminasRESUMEN
Herein, we present the case of accidental intravenous injection of gasoline in a 62-year-old male who was admitted to a dialysis center for his regular hemodialysis. Due to previous contact with another SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) positive patient, the hemodialysis was conducted in an isolated room. At the end of the procedure, the nurse, wearing all necessary personal protective equipment (PPE), in the intent to clean the dialysis catheter, applied medical gasoline, instead of 0.9% sodium chloride, intravenously to the patient. Soon afterwards, the patient's clinical condition deteriorated, and cardiopulmonary resuscitation was started. Despite the immediate reaction of the medical staff, after two successful cardiopulmonary reanimation and necessary intensive care measures, the patient suffered respiratory, metabolic, and lactic acidosis, hypotension, and tachyarrhythmia and ultimately died 7 h after the incident. The autopsy was conducted under the order of the district attorney. Main autopsy findings were marked congestion; right pleural and pericardial effusion; brain and lung edema; enlarged heart with left ventricle thickening and mild perivascular fibrosis; nephrosclerosis; tubular thyroidization; and interstitial fibrosis with inflammation. Gasoline presence was indisputably proven by conducted toxicology analysis in lung, bile, and brain samples. Traces of gasoline could be noted in the patient's blood sample in comparison to the blood that did not contain gasoline, but it was not possible to confidently claim that gasoline was present in the blood. Based on relevant findings, we concluded that the death of the patient was violent and that the cause of death was acute intoxication by gasoline.
Asunto(s)
Gasolina , Diálisis Renal , Humanos , Masculino , Persona de Mediana Edad , Gasolina/envenenamiento , Resultado Fatal , COVID-19 , Inyecciones Intravenosas , Pulmón/patologíaRESUMEN
Foreign body ingestion in children is a frequent cause for medical consultation. Although most foreign bodies are spontaneously eliminated from the gastrointestinal tract, life-threatening complications such as gastrointestinal obstruction or perforation can occur. We report the case of a 6-year-old boy who died 2 days after the onset of nausea and abdominal pain, with no foreign body ingestion witnessed or reported in the previous days. Autopsy showed a diffuse peritonitis and a perforation of the transverse colon caused by three high-powered magnets stacked together, and attached to the outer stomach wall via a fourth magnet located in the stomach. The cause of death was peritonitis due to bowel perforation by ingested magnets, which were shown to have come from a toy belonging to the child. Ingestion of multiple high-powered magnets carries a high risk of gastrointestinal complications and can exceptionally have a fatal outcome, especially as it often goes unreported and causes non-specific gastrointestinal symptoms that can delay diagnosis and management. This case highlights the need to raise public awareness of the potential risks of ingesting such magnets and to strengthen safety standards to protect children from this serious health hazard.
Asunto(s)
Cuerpos Extraños , Perforación Intestinal , Imanes , Peritonitis , Humanos , Masculino , Niño , Perforación Intestinal/etiología , Cuerpos Extraños/complicaciones , Imanes/efectos adversos , Peritonitis/etiología , Juego e Implementos de Juego , Resultado Fatal , Estómago/patología , Colon Transverso/patologíaRESUMEN
A senile male black capuchin monkey (Sapajus nigritus) kept under human care in a Zoo was found dead after 2 weeks presenting signals of weight loss and hyporexia. Histopathological revealed a necrotizing encephalitis. Although it was not observed microscopically, Sarcocystis sp infection was detected in brain tissue from molecular assays. These infections have been rarely described in neotropical primates, particularly associated with tissue lesions.
Asunto(s)
Enfermedades de los Monos , Sarcocystis , Sarcocistosis , Animales , Sarcocistosis/veterinaria , Sarcocistosis/diagnóstico , Sarcocistosis/parasitología , Sarcocystis/aislamiento & purificación , Sarcocystis/genética , Enfermedades de los Monos/parasitología , Enfermedades de los Monos/diagnóstico , Masculino , Animales de Zoológico , Resultado Fatal , Encefalitis/veterinaria , Encefalitis/parasitología , Encefalitis/diagnóstico , SapajusRESUMEN
PURPOSE: Candida auris, an emerging multidrug-resistant yeast, has been reported worldwide. In Italy, the first case was reported in 2019. We describe the first case of C. auris, imported from Greece, in Milan, using whole genome sequencing to characterise mutations associated with antifungal resistance. CASE PRESENTATION: On October 2022 an 80-year-old Italian man was hospitalised in Greece. In the absence of clinical improvement, the patient was transferred to our hospital, in Italy, where blood culture resulted positive for C. auris. Despite therapy, the patient died of septic shock. In a phylogenetic analysis the genome was assigned to Clade I with strains from Kenya, United Arab Emirates and India. D1/D2 region resulted identical to a Greek strain, as for many other strains from different World regions, highlighting the diffusion of this strain. CONCLUSION: Importation of C. auris from abroad has been previously described. We report the first case of C. auris imported into Italy from Greece, according to phylogenetic analysis. This case reinforces the need for monitoring critically ill hospitalised patients also for fungi and addresses the need for the standardisation of susceptibility testing and strategies for diagnosis and therapy.
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Antifúngicos , Candida auris , Candidiasis , Filogenia , Humanos , Masculino , Italia , Anciano de 80 o más Años , Grecia , Candidiasis/microbiología , Candidiasis/tratamiento farmacológico , Candidiasis/diagnóstico , Antifúngicos/uso terapéutico , Candida auris/genética , Secuenciación Completa del Genoma , Enfermedades Transmisibles Importadas/microbiología , Enfermedades Transmisibles Importadas/diagnóstico , Resultado Fatal , Pruebas de Sensibilidad Microbiana , Candidiasis InvasivaRESUMEN
Erdheim-Chester disease (ECD) is a rare 'L' (Langerhans) group histiocytic neoplasm that affects a multitude of organ systems, causing osteosclerotic bone lesions, periaortic encasement ('coated' aorta), retroperitoneal fibrosis involving kidneys and ureters ('hairy kidney'), and infiltration of the central nervous system. Cardiovascular involvement can occur in up to 70% of patients and is usually found during computed tomography/magnetic resonance imaging evaluation. When present, cardiovascular symptoms can have wide variability in presentation from asymptomatic to pericarditis, fatal cardiac tamponade, myocardial infarction, conduction abnormalities, heart failure, renal artery stenosis, and claudication. Cardiac involvement found on imaging includes right atrial pseudotumor, right atrioventricular groove infiltration, and pericardial effusions. ECD can involve the large- and medium-sized arteries, often seen as periarterial thickening (commonly coating the aorta) with stenosis/occlusion. Although more cardiovascular ECD cases have begun to be published in the literature, more data are needed on the outcomes of these patients, as well as how cardiovascular manifestations respond to treatment of ECD.
Asunto(s)
Enfermedad de Erdheim-Chester , Humanos , Enfermedad de Erdheim-Chester/complicaciones , Enfermedad de Erdheim-Chester/diagnóstico , Enfermedad de Erdheim-Chester/tratamiento farmacológico , Enfermedad de Erdheim-Chester/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Femenino , Anciano , Resultado Fatal , Resultado del TratamientoRESUMEN
Infective native aneurysms (INA) of the infrapopliteal arteries are rare and have previously been poorly described. This systematic review aims to provide an overview of the literature of this entity. Furthermore, two case reports of our own clinical experience are presented. PubMed, ScienceDirect, Cochrane, Ovid Embase, Ovid MEDLINE, and Web of Science were searched for articles on INAs of the infrapopliteal segment from January 1990 to September 2023. Article screening and selection were performed adhering to PRISMA guidelines. A total of 98 articles were screened and 20 were eligible for inclusion, of which all were case reports. In total, 22 patients with 28 infrapopliteal INAs were identified. The majority of INAs were located in the tibioperoneal trunk (n = 10, 36%) followed by the posterior tibial artery (n = 7, 25%). A current, or history of, infective endocarditis (IE) was described in 18 out of 22 patients (82%). Two patients died during hospitalization and one patient required a transfemoral amputation. A conservative antibiotic-only approach was chosen in three out of 28 INAs, two of which were the case reports described in this article; surgical or endovascular intervention was performed in 19 out of 28 aneurysms. No complications occurred in the conservative group, but one complication (transfemoral amputation) occurred in the interventional group. Infrapopliteal INA is a rare entity, and most described cases are precipitated by IE. Surgery or endovascular treatment might be indicated, but more research is warranted to define which patient would benefit and by what surgical approach.
Asunto(s)
Aneurisma Infectado , Antibacterianos , Arteria Poplítea , Humanos , Arteria Poplítea/cirugía , Arteria Poplítea/diagnóstico por imagen , Arteria Poplítea/microbiología , Aneurisma Infectado/microbiología , Aneurisma Infectado/cirugía , Aneurisma Infectado/diagnóstico por imagen , Aneurisma Infectado/diagnóstico , Aneurisma Infectado/mortalidad , Aneurisma Infectado/terapia , Masculino , Femenino , Anciano , Persona de Mediana Edad , Resultado del Tratamiento , Antibacterianos/uso terapéutico , Procedimientos Endovasculares/efectos adversos , Anciano de 80 o más Años , Factores de Riesgo , Amputación Quirúrgica , Adulto , Resultado FatalRESUMEN
BACKGROUND: Tuberculosis (TB), one of the leading causes of death worldwide, has a higher incidence among indigenous people. Albeit uncommon, autoimmune hemolytic anemia (AIHA) has been deemed a risk condition to develop mycobacterial infection, as a result of the immunosuppressive treatments. TB, in turn, can be a predisposing factor for secondary infections. CASE PRESENTATION: Here we present a case of a 28-year-old indigenous woman from Colombia, previously diagnosed with AIHA and pulmonary TB. Despite various treatments, therapies and medical interventions, the patient died after severe medullary aplasia of multiple causes, including secondary myelotoxicity by immunosuppressive therapy and secondary disseminated infections, underlining infection by Staphylococcus aureus, Klebsiella pneumoniae and Candida glabrata, which were identified as drug-resistant microorganisms. Together, this led to significant clinical complications. Invasive aspergillosis was diagnosed at autopsy. CONCLUSIONS: This report presents a rarely finding of AIHA followed by TB, and highlights the great challenges of dealing with co-infections, particularly by drug resistant pathogens. It also aims to spur governments and public health authorities to focus attention in the prevention, screening and management of TB, especially among vulnerable communities, such as indigenous people.
Asunto(s)
Anemia Hemolítica Autoinmune , Coinfección , Humanos , Femenino , Adulto , Coinfección/microbiología , Resultado Fatal , Anemia Hemolítica Autoinmune/complicaciones , Colombia , Klebsiella pneumoniae/aislamiento & purificación , Staphylococcus aureus/aislamiento & purificación , Candida glabrata/aislamiento & purificación , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/microbiología , Infecciones Estafilocócicas/microbiología , Pueblos Indígenas , Candidiasis/tratamiento farmacológico , Candidiasis/microbiologíaRESUMEN
BACKGROUND: The incidence of Talaromyces marneffei (T. marneffei) infection has increased in recent years with the development of organ transplantation and the widespread use of immunosuppressive agents. However, the lack of clinical suspicion leading to delay or misdiagnosis is an important reason for the high mortality rate in non-human immunodeficiency virus (HIV) and non-endemic population. Herein, we report a case of disseminated T. marneffei infection in a non-HIV and non-endemic recipient after renal transplant, who initially presented with skin rashes and subcutaneous nodules and developed gastrointestinal bleeding. CASE PRESENTATION: We describe a 54-year-old renal transplantation recipient presented with scattered rashes, subcutaneous nodules and ulcerations on the head, face, abdomen, and right upper limb. The HIV antibody test was negative. The patient had no obvious symptoms such as fever, cough, etc. Histopathological result of the skin lesion sites showed chronic suppurative inflammation with a large number of fungal spores. Subsequent fungal culture suggested T. marneffei infection. Amphotericin B deoxycholate was given for antifungal treatment, and there was no deterioration in the parameters of liver and kidney function. Unfortunately, the patient was soon diagnosed with gastrointestinal bleeding, gastrointestinal perforation and acute peritonitis. Then he rapidly developed multiple organ dysfunction syndrome and abandoned treatment. CONCLUSIONS: The risk of fatal gastrointestinal bleeding can be significantly increased in kidney transplant patients with T. marneffei infection because of the long-term side effects of post-transplant medications. Strengthening clinical awareness and using mNGS or mass spectrometry technologies to improve the detection rate and early diagnosis of T. marneffei are crucial for clinical treatment in non-HIV and non-endemic population.